Nuclear factor XIIIa staining (clone AC‐1A1 mouse monoclonal) is a sensitive and specific marker to discriminate sebaceous proliferations from other cutaneous clear cell neoplasms

Sebaceous carcinoma is a rare but serious malignancy that may be difficult to diagnose when poorly differentiated. Other epithelial tumors with clear cell change may mimic sebaceous carcinoma. Few useful or specific immunohistochemical markers for sebaceous differentiation are available. Nuclear staining with factor XIIIa (clone AC‐1A1) was recently found to be a highly sensitive marker of sebaceous differentiation. We evaluated nuclear factor XIIIa (AC‐1A1) staining in sebaceous neoplasms vs. other cutaneous clear cell tumors. We stained 27 sebaceous proliferations: sebaceous hyperplasia (7), sebaceous adenoma (8), sebaceoma (5), sebaceous carcinoma (7). We also stained 67 tumors with clear cell change: basal cell carcinoma (8), squamous cell carcinoma (8), hidradenoma (7), desmoplastic trichilemmoma (2), trichilemmoma (10), trichilemmal carcinoma (3), clear cell acanthoma (9), atypical fibroxanthoma (1), syringoma (8), trichoepithelioma (1), metastatic renal cell carcinoma (2), and nevi with balloon cell change (8). Nuclear factor XIIIa (AC‐1A1) staining was present in 100% of sebaceous proliferations; 96% displayed strong staining. Non‐sebaceous clear cell tumors were negative or only weakly positive with factor XIIIa (AC‐1A1) in 95.5%; only 4.5% showed strong staining. This suggests that strong nuclear factor XIIIa (AC‐1A1) staining is a sensitive and specific marker of sebaceous neoplasms vs. other clear cell tumors.     

Immunohistologic differential diagnosis of basal cell carcinoma, squamous cell carcinoma, and trichoepithelioma in small cutaneous biopsy specimens

The distinction between squamoid basal cell carcinoma and basaloid squamous cell carcinoma (or between BCC and trichoepithelioma variants) is usually made readily on the basis of defined histological criteria. However, these differential diagnoses occasionally can pose difficult morphological problems. The stated distinctions are clinically important because the risk of progressive disease is significantly higher with squamous carcinoma of the skin than with basal cell carcinoma (BCC), and a trichoepithelioma misinterpreted as BCC burdens the patient with an inaccurate diagnosis that may result in inappropriate surgery. Recent reports have suggested that reactivity with the monoclonal antibody Ber-EP4 is capable of separating histologically similar basal cell and squamous carcinomas, and that ihe expression of bcl-2 or CD34 antigen is able to distingtush BCC from trichoepithelioma. However, corroborative studies of these contentions are few in number. In order to investigate the usefulness of the stated immunostains in the above-cited differential diagnoses, the authors analyzed 45 basal cell carcinomas and 22 squamous carcinomas, as well as 36 trichoepitheliomas. The monoclonal antibodies Ber-EP4, My10 (CD34), and anti-bcl-2 were applied to formalin-fixed paraffin sections in all cases, using a standard avidin-biotin-peroxidase complex method. Most BCCs demonstrated strong, diffuse cytoplasmic labeling with Ber-EP4 and anti-bcl-2. In contrast, the squamous carcinomas were uniformly negative for the former marker and only focally reactive for the latter in four examples. ‘Peripheral’bcl-2 staining of trichoepitheliomas was noted in 24 of 33 of the immunoreactive tumors, but the remainder were marked diffusely and similarly to most BCCs. Among the latter, immature trichoepitheliomas were diffusely reactive for this marker in 6 of 8 cases. Labeling of epithelium for CD34 failed to discriminate between any of the tumor types under evaluation, whereas staining of peritumoral stroma was characteristic of the majority of trichoepitheliomas and more than one-third of metatypical basal cell carcinomas. These data support the suggestion that Ber-EP4 and bcl-2 are useful in the separation of BCC from squamous carcinomas. Nevertheless, they also serve to caution against reliance upon bcl-2 and CD34 immunostains in attempting to distinguish BCC from trichoepithelioma in histologically enigmatic cases. There is currently no certain method other han conventional microscopy that can be applied successfully to the latter problem.     

Basal cell carcinoma with sebaceous differentiation

Some authors have used sebaceous epithelioma as a synonym for basal cell carcinoma (BCC) with sebaceous differentiation. However, our review of the literature revealed that definite cases of BCC with sebaceous differentiation that provide adequate clinical and histopathologic information are scarce. We present the case of a 72-year-old woman with a pigmented nodular lesion on her right ala nasi region, clinically diagnosed as pigmented BCC. Histopathologically, this nodular lesion, which was completely excised, showed typical features of BCC. It was noteworthy that within one aggregation of the presented BCC, tiny and small duct-like structures lined by cornified layers with a crenulated inner surface were seen. Vacuolated cells were scattered within a few aggregations, and they had foamy, bubbly cytoplasm and starry nuclei. The vacuolated cells were immunohistochemically positive for epithelial membrane antigen (EMA). These histopathologic findings demonstrated unquestionable sebaceous differentiation in this BCC, namely BCC with sebaceous differentiation, which should be distinguishable from both sebaceoma and sebaceous carcinoma. The small duct-like structures lined by eosinophilic cuticle, indicating apocrine differentiation, were also observed in this BCC.     

Immunolabeling pattern of cytokeratin 19 expression may distinguish sebaceous tumors from basal cell carcinomas

Background:  Distinction between sebaceous tumors and basal cell carcinomas can often pose diagnostic problems. Recent work with the antibody to cytokeratin 19 (CK 19) has shown that this marker has high specificity for undifferentiated basaloid cells. Our aim was to evaluate the use of CK 19 staining patterns in differentiating between sebaceous tumors and basal cell carcinomas. The sebaceous tumors that were examined in this study included sebaceous adenomas, sebaceous epitheliomas (sebaceomas) and sebaceous carcinomas.
Methods:  Thirty-seven cases including 5 sebaceous adenomas, 16 sebaceous epitheliomas, 6 sebaceous carcinomas and 14 basal cell carcinomas (7 being of the morpheaform type and 7 nodular basal cell carcinomas) were tested with a monoclonal mouse antibody to human CK 19.
Results:  CK 19 was focally positive in 1/5 (20%) sebaceous adenomas, 8/16 (50%) of sebaceous epitheliomas and 1/6 (17%) of sebaceous carcinomas. Strongly positive expression of CK 19 was not seen in any of the sebaceous adenoma, sebaceous epithelioma or sebaceous carcinoma specimens. CK 19 was found to be strongly positive in 9/14 (64%) and focally positive in 2/14 (14%) of basal cell carcinomas.
Conclusion:  CK 19 expression can be helpful in differentiating sebaceous tumors (including sebaceous adenomas, sebaceous epitheliomas and sebaceous carcinomas) from basal cell carcinomas and may be a useful adjunct when these entities are included in the differential diagnosis.     

Does the peritumoral stroma of basal cell carcinoma recapitulate the follicular connective tissue sheath?

Background: There are compelling embryologic and anatomic relationships within adnexal tumors. However, these are mostly perceived within the epithelial component while the stromal component of the tumors is frequently overlooked. In postnatal skin, nestin is almost exclusively expressed in the perifollicular mesenchyme. This study examines the expression of this neuroepithelial stem cell protein in trichoblastoma/trichoepithelioma and in basal cell carcinoma (BCC), which is increasingly being viewed as follicular in nature. Methods: We employed standard immunohistochemical methods with three different antibodies to examine the expression of nestin in 25 BCCs and compared the staining pattern with that of 7 trichoblastomas and 11 trichoepitheliomas. Results: Nestin is expressed in the peritumoral stroma of all tumors examined and is limited to the immediate layer of mesenchymal cells surrounding the tumor epithelium. In BCC, nestin‐immunoreactive cells are found as a sheath of thin, spindled fibroblasts, while reactive cells are plump in trichoepitheliomas/trichoblastomas. Conclusions: We postulate that the peritumoral stroma of BCC imitates the perifollicular connective tissue sheath, while in contrast that of trichoepithelioma/trichoblastoma is similar to the papillary and immediate peripapillary follicular mesenchyme. Further functional and animal experimental studies are needed to test this hypothesis. Sellheyer K, Krahl D. Does the peritumoral stroma of basal cell carcinoma recapitulate the follicular connective tissue sheath? A comparative analysis of nestin expression in basal cell carcinoma, trichoepithelioma, trichoblastoma and the hair follicle.     

Muir-Torre syndrome: a case of this uncommon entity

A 69-year-old Hispanic woman presented for the evaluation of nodules on the head and back. In the past, she had been treated for basal cell carcinoma (BCC) of the face; the referring physician was concerned that the new lesions might also be BCC. The patient had an extensive past medical history. In addition to BCC, she had been treated for breast cancer, colon cancer, and cervical cancer prior to emigrating to the USA. Her colonic malignancy had been localized proximal to the splenic flexure. She also had a history of colonic polyps and distal colonic villous adenoma. She denied ever being treated with radiation. Further details of her medical history and cancer staging were not available. Her family history was significant for a sister with colon cancer and transitional cell carcinoma of the urinary bladder. In addition, she had a great aunt with oral cancer and a great uncle with lung cancer. Neither the patient or her relatives had any history of tobacco use. On physical examination, in addition to scars from a radical mastectomy and midline abdominal laparotomy, four skin lesions were noted: two on the scalp, one on the tragus, and one on the mid-back. The first lesion on the vertex of the scalp was a yellow-brown waxy papule measuring 0.6 x 0.5 cm. This lesion was similar to that on the mid-back, except in size. The lesion on the back measured 1.2 x 1.0 cm. The second lesion on the frontal scalp measured 0.8 x 0.6 cm and was red-brown with a pearly appearance and some central hyperkeratosis. The tragus lesion was similar in appearance to that on the frontal scalp. Shave biopsies of all lesions were obtained. The lesions on the scalp and mid-back revealed lobules of sebaceous cells in the dermis with a minority of surrounding basaloid cells, consistent with a diagnosis of sebaceous adenoma (Fig. 1). Although the lesion on the frontal scalp also showed sebaceous differentiation, there were a greater number of basaloid cells, some with hyperchromatic nuclei and mitotic figures; this was consistent with a diagnosis of sebaceous epithelioma (Fig. 2). The final lesion (tragus) was histologically consistent with a keratotic BCC. No further treatment was required for these benign sebaceous tumors, but their presence defined our patient's condition as Muir-Torre syndrome. Mohs' micrographic surgery was performed on the tragus BCC and the margins were tumor free in one stage. The patient returned 1 year later with a lesion anterior to the left axilla which was biopsied to rule out BCC (Fig. 3). Histologically, this lesion was also consistent with sebaceous epithelioma.     

Muir-Torre-Syndrom mit bisher nicht beschriebener Frameshift-Mutation im MSH2-Gen

Muir-Torre syndrome (MTS) is a rare phenotypic variant of hereditary non-polyposis colorectal carcinoma (HNPCC, Lynch syndrome), in which patients, in addition to visceral carcinomas, develop skin tumors. Multiple keratoacanthomas and basal cell carcinomas with sebocytic differentiation are characteristic as well as multiple benign and malignant tumors of the sebaceous glands, such as sebaceous adenoma, sebaceous epithelioma (sebaceoma) and sebaceous carcinoma. Particularly Cystic tumors of the sebaceous glands are especially suggestive of MTS. In genetically predisposed persons, cutaneous and visceral tumors are diagnosed at an average age of 53 years. Here we present an interesting case of a 65-year-old man in whom molecular genetic tests revealed a novel mutation in the MSH2 gene, leading to a frame shift within the gene.     

Complex adnexal tumor of the primary epithelial germ with distinct patterns of superficial epithelioma with sebaceous differentiation, immature trichoepithelioma, and apocrine adenocarcinoma.

A 60-year-old man came for treatment of a sharply outlined erythematous plaque on the gluteal area (45 x 20 mm) of 20 years' duration. Eccentrically located on the plaque was a nodule, 20 mm in diameter. Histological study of the plaque showed a superficial platelike tumor with basaloid bland cytology and sebaceous gland differentiation. Histologic study of the nodule found an undifferentiated adenocarcinoma whose ductlike glandular structures opened to the skin surface and infiltrated the whole depth of the dermis. Study of other areas of the lesion detected two more neoplasms. A nodule of squamous cell carcinoma was found within the superficial band of the benign sebaceous tumor. The fourth neoplastic pattern consisted of epithelial islands composed of basaloid cells within a fibroblastic stroma. There was prominent palisading of epithelial cell nuclei at the periphery of the islands, which usually were surrounded by a sheath of mesenchymal cells. In this complex adnexal tumor of the primary epithelial germ, sebaceous and follicular differentiation both simulate neoplastic patterns recently described as separate entities: superficial epithelioma with sebaceous differentiation and immature trichoepithelioma. The undifferentiated adenocarcinoma may represent differentiation toward the third component of the germ, that is, the apocrine gland.     

Expression of α‐methylacyl‐CoA racemase (P504S) in sebaceous neoplasms

Background: α‐Methylacyl‐CoA racemase (AMACR), also known as P504S, is a protein that plays an important role in mitochondrial and peroxisomal β‐oxidation of branched‐chain fatty acid and bile acid intermediates. AMACR has been established as a valuable diagnostic marker for prostate cancer and has recently been shown to be useful in the diagnosis of colorectal carcinoma. Despite the importance of lipid metabolism in sebum production by sebaceous glands of the skin, there are no studies evaluating the expression of AMACR in sebaceous neoplasms. Methods: Five samples of normal sebaceous glands as well as five cases each of sebaceous hyperplasia (SH), sebaceous adenoma (SA), basal cell carcinoma (BCC) with sebaceous differentiation and extraocular sebaceous carcinoma (SC) were evaluated for immunohistochemical (IHC) expression of AMACR. Each case was reviewed by a single dermatopathologist and graded using a semi‐objective grading schema. Results: Normal sebaceous glands showed strong (4+) expression of AMACR. Among sebaceous neoplasms, SH showed the highest expression (4+), SA and BCC with sebaceous differentiation showed varied expression (2+ and 1+, respectively), and extraocular SC showed no expression of AMACR. Conclusions: The expression of AMACR is increased in benign sebaceous glands and SH; with decreasing AMACR expression in tumors with less sebaceous differentiation (i.e. SA and SC). These findings provide insight into the potential pathogenesis of sebaceous neoplasms while assisting in the microscopic distinction of SA from SC. Halsey MA, Calder KB, Mathew R, Schlauder S, Morgan MB. Expression of α‐methylacyl‐CoA racemase (P504S) in sebaceous neoplasms.     

Ber-EP4 is a useful marker for follicular germinative cell differentiation of cutaneous epithelial neoplasms

Ber-EP4 is a monoclonal antibody that recognizes 34-kDa and 39-kDa non-covalently linked glycopolypeptides expressed by most human epithelial cells and carcinomas. In this study, we performed immunohistochemical staining of 31 cases of basal cell carcinoma (BCC); 20 cases of trichoblastoma (TB), including ten cases of nodular type, eight cases of cribriform type (trichoepithelioma) and two cases of columnar type (desmoplastic trichoepithelioma); 16 cases of actinic keratosis (AK); and 10 cases each of Bowen's disease, poroma and seborrheic keratosis. Six cases of BCC and AK were co-lesions of both neoplasms. In normal skin tissue, Ber-EP4 reacted positively with the secretory portion of eccrine glands and follicular germinative cells at the lower end of catagen hairs. Neoplastic cells in 97% of cases with BCC reacted positively with Ber-EP4 in at least 5% of neoplastic cells. Those in 90% with nodular type TB and 50% with trichoepithelioma also reacted positively in at least 5% of neoplastic cells. No cases of poroma, seborrheic keratosis, AK or Bowen's disease were immunohistochemically positive for Ber-EP4 in neoplastic cells. In all six cases with co-lesions of BCC and AK, neoplastic cells of BCC reacted positively with Ber-EP4 and those of AK were negative. Immunohistochemical examination using the Ber-EP4 antibody is a useful tool for diagnosing neoplasms with follicular germinative differentiation, such as TB, TE or BCC, and for differentiating those from squamous cell carcinoma in situ, poroma or seborrheic keratosis.     

Recent advances and controversies concerning adnexal neoplasms.

This article reviews the diagnostic clinical and histologic features of a group of adnexal tumors, including papillary eccrine adenoma, adenoid cystic carcinoma, Merkel's cell carcinoma, aggressive digital papillary adenoma (and adenocarcinoma), Bowen's disease, intraepidermal epithelioma, microcystic adnexal carcinoma and related tumors, and subcutaneous trichoepithelioma. These are adnexal tumors either often not recognized, because of their rarity, or the origin, biologic potential, and classification of which have been controversial.     

Malignant melanoma and nonmelanoma skin cancers in Northrhine-Westphalia, Germany: a patient- vs. diagnosis-based incidence approach

BACKGROUND: Dermatologists have repeatedly criticized that the public health importance of nonmelanoma skin cancers is not appropriately reflected by the patient-based cancer incidence rates of population-based cancer registries. The aims of this study were to estimate the patient incidence rates of squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and skin melanoma, and to study the effect of multiple primary skin tumors on the incidence rates. METHODS: We used a network of physicians covering a population of about 75,000 individuals to register all newly diagnosed invasive skin cancers (996 diagnoses in 796 patients), including BCC, SCC, and skin melanoma, from July 1998 to June 2003. We calculated age-standardized (world standard population) incidence rates (cases per 100,000 person-years) for the first diagnoses (called "patient incidence") and for any diagnoses of BCC, SCC, and skin melanoma (called "case incidence"). RESULTS: The patient incidence rates of BCC were 63.6 in men and 54.0 in women, and the case incidence rates of BCC were 82.7 and 71.1, respectively. The patient incidence rates of SCC were 17.4 in men and 9.7 in women, and the case incidence rates were 20.4 and 10.2, respectively. The patient and case incidence rates of skin melanoma were about the same at 13.6 in men and 18.5 in women. Twenty-five per cent of the BCC patients and 14% of the SCC patients suffered from more than one BCC and SCC, respectively, during the 5-year period. CONCLUSIONS: Patient incidence rates of BCC and SCC substantially underestimate the burden of nonmelanoma skin cancer in the population.     

七种细胞角蛋白在皮肤上皮性肿瘤中的表达

目的 观察7种细胞角蛋白在皮肤上皮性肿瘤中的表达,并探讨其意义.方法 应用免疫组化S-P法对54例不同的皮肤上皮性肿瘤和20例正常皮肤进行细胞角蛋白7(K72.2)、细胞角蛋白8(C-51)、细胞角蛋白10(DE-K10)、细胞角蛋白14(LL002)、细胞角蛋白17(E3)、细胞角蛋白18(DC10)、细胞角蛋白19(KS19.1)标记,观察不同细胞角蛋白的表达.结果 54例皮肤上皮性肿瘤包括,鳞状细胞癌10例、基底细胞癌10例、毛发肿瘤19例、皮脂腺癌2例、汗腺肿瘤13例.皮肤上皮性肿瘤中7种细胞角蛋白的表达和分布有所不同.鳞状细胞癌、基底细胞癌和毛发分化的肿瘤中细胞角蛋白多数呈弥漫表达;而汗腺分化的肿瘤中,不同部位表达不同细胞角蛋白,每种肿瘤各有特点.结论 选择地检测一组细胞角蛋白的联合表达,有助于皮肤上皮性肿瘤的诊断和鉴别诊断.     

PHLDA1 (TDAG51) is a follicular stem cell marker and differentiates between morphoeic basal cell carcinoma and desmoplastic trichoepithelioma

Background Morphoeic basal cell carcinoma (BCC) and desmoplastic trichoepithelioma can often be difficult to differentiate on routine sections and few reliable immunohistochemical markers are currently available. Recent cDNA microarray studies revealed the pleckstrin homology‐like domain, family A, member 1 protein (PHLDA1) as a highly reliable marker of the hair follicle stem cells. Given the differentiation of trichoepithelioma along the follicular lineage and the proposed role of PHLDA1 as a follicular stem cell marker, we examined the staining pattern of PHLDA1 in the desmoplastic variant of trichoepithelioma and in its differential diagnostic conundrum, morphoeic BCC. Objectives To describe the expression pattern of PHLDA1 in morphoeic BCC and desmoplastic trichoepithelioma. Methods Evaluation of the staining pattern for PHLDA1 was performed using standard immunohistochemical techniques. For comparison reasons, we analysed staining for PHLDA1 in normal skin structures with particular reference to the hair follicle. Results With the exception of one case, all 16 desmoplastic trichoepitheliomas were immunoreactive with more than 80% of the cells stained, whereas all 14 morphoeic BCCs were PHLDA1‐negative with the exception of ulcerated tumours. In the latter, the tumour islands close to the ulcer were PHLDA1‐positive whereas the deeper located tumour portions remained immunonegative. PHLDA 1 was prominently expressed in the hair follicle bulge of terminal and vellus hair follicles. Conclusions The hair follicle bulge marker PHLDA1 differentiates between desmoplastic trichoepitheliomas and nonulcerated examples of morphoeic BCCs. We suggest incorporating PHLDA1 in the diagnostic work‐up of difficult to differentiate basaloid tumours.     

Lacrimal caruncle primary basal cell carcinoma: case report and review

BACKGROUND: Basal cell carcinoma (BCC) is a common malignant skin neoplasm. The surface of the caruncle contains sebaceous glands, hair follicles, and lacrimal and sweat gland elements. Consequently, the caruncle may spawn any neoplasm that occurs in the conjunctiva, skin, or lacrimal gland. We report a patient with a primary BCC located on the lacrimal caruncle. METHODS: An 80-year-old man with a 5-month history of a gradually enlarging left caruncular neoplasm was seen. The lesion was nodular and irregularly brown-black colored, with no involvement of adjacent conjunctiva or skin. He had a history of sun exposure, but no personal or family history of other malignant neoplasms. RESULTS: The mass was excised completely. Histopathologic examination revealed a BCC originating in the basal layer of the conjunctival epithelium. No tumor recurrence has been noted after 7 years of follow-up. Primary BCC of the caruncle is unusual, and only four cases have been described in the PubMed. BCC should be considered in the differential diagnosis of caruncle and adjacent skin lesions.     

Basal cell carcinoma of the sole

Basal cell carcinoma (BCC) of the plantar surface of the foot is rare, with only 22 previously reported cases. This clinico-pathologic study is based on 20 cases pf BCC of the plantar surface and plantar-like surfaces from adjacent lower lateral and medial aspects of the foot, submitted to a large podiatric laboratory from 1986 through June 1992 (total specimens for this period = 518,624; total BCC of lower extremities, below knee = 53). There were 15 women and 5 men. The average patient age was 73 years, with a range from 52 to 92 years. The duration of the lesion before diagnosis was 2 months to 12 years, with an average of 2 years. Three patients had a history of trauma. Podiatric clinical diagnoses included BCC (4), SCC (3), soft tissue tumor (2), nevus (1), granuloma (1), keratosis (2), verucca (1), and psoriasis (1). Follow-up information was available on 10 patients; all were free of disease up to 64 months, with an average follow-up of 15.7 months. Three of 20 BCC showed predominant histologic patterns characteristic of fibroepithelioma of Pinkus (FEP). An additional three BCC showed focal or suggestive patterns of FEP. Fourteen tumors showed ordinary BCC histologic patterns. No multicentric-superficial or morphea like BCC were observed. The relatively high incidence of FEP in BCC of the sole correlates with abundant sweat glands and lack of hair follicles on the plantar surface, in accordance with the recent proposal that FEP derives its histologic pattern from the spread of BCC down eccrine ducts, eventually replacing them with solid strands of tumor.     

Histopathological review of sebaceous carcinoma of the eyelid

BACKGROUND: Sebaceous carcinoma of the eyelid can clinically mimic benign conditions, such as recurrent chalazion and inflammation and histopathologically squamous cell and basal cell carcinoma (BCC). This retrospective study was undertaken as an attempt to improve the characterization and consequently the diagnosis of these tumors. METHODS: Retrospective analysis was performed on eyelid specimens diagnosed as sebaceous carcinoma retrieved from Henry C. Witelson Ophthalmic Pathology Registry, Canada and Hospital Luis S. Bulnes Pathology Registry, Mexico. Two independent, masked pathologists reviewed the H&E microslides. RESULTS: Forty-four cases were retrieved, 31 from Canada and 13 from Mexico. Cytoplasmic vacuoles were observed in 48% of the cases. Eighty-four percent of the cases were classified as poorly differentiated lesions. Of these, 75% had features similar to squamous cell carcinoma (SqCC), some with dyskeratosis (30%) and 7% resembled BCC. Solid growth pattern was seen in 26.2% of the cases and lobular growth pattern in 26.2%. Superficial spread resembling Bowen-like disease was observed in 33% of the cases, pagetoid features in 33% and comedocarcinoma in 31.8%. CONCLUSION: Sebaceous carcinoma presented as a poorly differentiated lesion in most cases of this series, which suggests a possibility of misdiagnosis because of its similarities to SqCC.     

Fibroepithelioma of Pinkus is a true basal cell carcinoma developing in association with a newly identified tumour-specific type of epidermal hyperplasia

Background Fibroepithelioma of Pinkus (FEP) has long been viewed as a subtype of basal cell carcinoma (BCC). Recently, however, the proposal has been made that FEP represents a fenestrated trichoblastoma/trichoepithelioma. One of the main arguments is the presence of Merkel cells in FEP, which typically do not occur in BCC. Objectives As the new stem cell marker, PHLDA1 (TDAG51), labels trichoepithelioma but not BCC, our aim was to characterize its staining pattern in FEP. Because adnexal tumours have been viewed as recapitulating embryogenesis, we also examined PHLDA1 immunoreactivity in the skin of human embryos and fetuses. Methods We studied immunohistochemically PHLDA1 staining in 31 FEPs, 14 BCCs and 16 trichoepitheliomas and compared this with its staining pattern in embryonic skin and with the distribution of Merkel cells. Results In FEP, PHLDA1 labels the anastomosing network of thin cellular strands but not the basaloid nubbins. During embryogenesis, PHLDA1 stains the basal cell layer of the epidermis, as long as adnexal structures develop. Immunoreactivity for PHLDA1 correlates positively with the presence of Merkel cells. Conclusions We propose that the thin anastomosing network of PHLDA1‐positive cells represents a type of epidermal hyperplasia specific to FEP. The multifocal BCCs that are PHLDA1‐negative develop from this network which becomes incorporated into the tumour. Viewing the anastomosing network as a tumour‐specific form of epidermal hyperplasia explains the hitherto enigmatic presence of Merkel cells in FEP.